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Causal effect of kimchi intake on HDL-cholesterol levels in middle aged Korean men: a two-sample Mendelian
Jaehee Cha1, Seong-Hee Ko1, Dayeon Shin2
1Department of Food and Nutrition, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Republic of Korea.
Insights
Kimchi consumption may causally protect against low high-density lipoprotein cholesterol (HDL-C) in Korean men. This fermented food shows potential as a sex-specific dietary strategy for cardiovascular health.
Area of Science:
- Cardiovascular Epidemiology
- Nutritional Genomics
- Metabolic Health
Background:
- Low high-density lipoprotein cholesterol (HDL-C) is a significant risk factor for cardiovascular disease.
- Previous observational studies on kimchi and HDL-C are limited by confounding factors and reverse causality.
Purpose of the Study:
- To investigate the causal association between kimchi intake and HDL-C levels using Mendelian randomization (MR).
- To stratify analyses by sex to identify potential sex-specific effects.
Main Methods:
- Utilized data from two Korean Genome and Epidemiology Study (KoGES) cohorts (HEXA and Ansan/Ansung).
- Assessed kimchi intake via food frequency questionnaires and identified genetic variants (SNPs) associated with consumption.
- Employed multiple MR methods (IVW, MR-Egger, weighted median, MR-PRESSO) with sensitivity analyses to assess the causal effect.
Main Results:
- A significant inverse causal relationship was found between higher kimchi consumption and reduced HDL-C in men (IVW and MR-PRESSO analyses).
- No significant association was observed between kimchi intake and HDL-C levels in women.
- Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy.
Conclusions:
- Kimchi consumption demonstrates a causal effect in preventing HDL-C reduction among middle-aged Korean men.
- Findings suggest kimchi as a potential sex-specific dietary intervention for improving cardiovascular health.
Background:
High-density lipoprotein cholesterol (HDL-C) helps remove excess cholesterol, and low levels are a key metabolic risk factor for cardiovascular disease. Although several studies have investigated the association between kimchi consumption and HDL-C levels, these observational findings are often limited by confounding factors and reverse causality.
Objective:
We aimed to assess the causal association between kimchi intake and the reduced HDL-C using Mendelian randomization (MR), with analyses stratified by sex.
Methods:
We conducted this study using participants from two cohorts of the Korean Genome and Epidemiology Study (KoGES): the Health Examinees (HEXA) cohort (n = 53,060) and the Ansan/Ansung cohort (n = 4,907). Kimchi intake was assessed via a semi-quantitative food frequency questionnaire, estimating total daily consumption (g/day) of various kimchi types including baechu (cabbage) kimchi, kkakdugi/mu-kimchi, nabak-kimchi/dongchimi, and other varieties. Single nucleotide polymorphisms (SNPs) associated with kimchi consumption were identified via genome-wide association studies (GWAS), adjusting for covariates and applying a significance threshold of p < 5 × 10⁻⁵ and linkage disequilibrium cutoff (r² < 0.001). A total of 86 SNPs in men and 82 in women were selected as instrumental variables (IVs) for MR analysis. The MR analysis was conducted using inverse-variance weighted (IVW), MR-Egger, weighted median, and MR-PRESSO methods. Sensitivity analyses included heterogeneity testing, leave-one-out analysis, and funnel plot inspection.
Results:
In men, a significant causal relationship between higher kimchi consumption and lower odds of reduced HDL-C was identified by both the IVW (OR = 0.997, 95% CI = 0.996-0.999, p < 0.05) and MR-PRESSO (OR = 0.998, 95% CI = 0.996-0.999, p < 0.05) analyses, with no evidence of heterogeneity or horizontal pleiotropy. No significant associations were observed in women.
Conclusion:
This study provides evidence for a causal effect of kimchi consumption in preventing decreases in HDL-C levels among middle-aged Korean men. These findings support kimchi as a sex-specific dietary intervention for cardiovascular health.
